The pan-cancer landscape of abnormal DNA methylation and intratumor microorganisms

Microorganisms play very important roles in carcinogenesis, tumor progression, and resistance upon treatment. Due to the challenge of accurately acquiring samples and quantifying low-biomass tissue microorganisms, most studies have focused on the effect of gut microorganisms on cancer treatments, especially the efficacy of immunotherapy. Although recent publications reveal the potential interactions between intratumor microorganisms and the immune microenvironment, whether and to what extent the intratumor microorganism could affect progression and treatment outcome remain controversial. This study is aiming to evaluate the associations among intratumor microorganisms, DNA methylation cancer driver genes, immune response, and clinical outcomes from a pan-cancer perspective, using 6,876 TCGA samples across 21 cancer types. We revealed that tumor microorganism dysbiosis is closely associated with the abnormal tumor methylome and/or tumor microenvironment, which might serve to enhance the proliferation ability and fitness for the therapy of tumors. These findings shed the light on a better understanding of the interactions between tumor cells and carcinogens during and after tumor formation, as well as microorganism-associated methylation alterations that could further serve as biomarkers for clinical outcome assessment.